Altered resting functional network topology assessed using graph theory in youth with attention-deficit/hyperactivity disorder

Abstract

Notwithstanding an extensive literature about attention-deficit/hyperactivity disorder (ADHD) and brain structure and function, the controversy of ADHD resulting from dysfunction or developmental delay remains unclear. Graph analysis studies have reached consensus about the pattern of increased integration and decreased randomness during childhood and early adulthood. Here, we hypothesized that ADHD is a neurodevelopmental disorder resulting from developmental delay and would show a pattern of decreased integration and increased randomness during childhood and early adulthood compared with typically developing children. To test this hypothesis, publicly available resting-state fMRI data from 102 children with ADHD and 143 typically developing controls (TDC) were compared using graph theoretical analysis. Functional connectivity was estimated using Pearson correlation analysis, and network topology was characterized using small-world (SW) and minimum spanning tree (MST) properties. The mean strength of global connectivity was significantly weaker in those with ADHD and was related to ADHD diagnosis scores. Significant group differences were observed for SW(clustering coefficient, path length, global and local efficiency) and MST (leaf number, kappa and hierarchy) topology. In addition, except for global efficiency, all of these parameters showed significant correlations with ADHD-related disability. The topology of SW and MST showed less integration and more randomness, which confirmed that ADHD is a disorder associated with developmental delay. Moreover, the topology of resting-state functional networks in children with ADHD that show abnormalities was associated with the degree of disability, which can be considered neurological hallmarks of neurodevelopmental disorders and may facilitate the evaluation and monitoring of clinical status in individuals with ADHD.